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ABSTRACT: Some 2,3,5,10-tetrahydrobenzo[g]isoquinoline-3,5,10-triones 2 were prepared by a Diels-Alder reaction between different 2-azadienes 1 and 1,4-naphthoquinone. The corresponding N- and O-methyl derivatives 3 and 4 respectively were obtained by the use of CH3I in a basic medium: triethylamine (method A), K2CO3 and tris[2-(2-methoxyethoxy)ethylamine] (method B) or in the presence of Ag2O. The reaction of N-methylation was regiospecific, while the O-methylation was regioselective. - The in vitro cytotoxic activity of the prepared compounds was evaluated against murine L 1210 leukemia cells and a human tumor cell line MDA-MB 231. A weak, not significant activity was observed (IC50 values are ranging from 6 to > 10 μg/ml).N- und O-methylierte Derivate von 2,3,5,10-Tetrahydrobenzo[g]isochinolin-3,5,10-trionenEinige 2,3,5,10-Tetrahydrobenzo[g]isochinolin-3,5,10-trionen 2 wurden durch Diels-Alder Reaktion zwischen verschiedenen 2-Azadienen 1 und 1,4-Naphtoquinonen hergestellt. Die entspr. N- und O-methylierten Derivate wurden jeweils mit CH3I in basischem Reaktionmedium: Triethylamin (Methode A), K2CO3 und Tris[2-(2-Methoxyethoxy)ethylamin] (Methode B) oder mit Ag2O erhalten. Die N-Methylierung ist regiospezifisch, die O-Methylierung ist regioselektiv. - Die cytotoxische in vitro Aktivität der hergestellten Verbindungen wurde an Leukämie-Zellen der Maus und an menschlichen Tumorzellen MDA-MB 231 untersucht. Eine schwache, nicht signifikante Wirkung wurde beobachtet (die IC50 Werte schwanken zwischen 6 und > 10 μg/ml).
Archiv der Pharmazie 09/2006; 326(9):547 - 550. · 1.71 Impact Factor
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ABSTRACT: Boc-aminoethylindoloquinone 8, a key intermediate for the building of pentacyclic quinoneimines, analogues of kuanoniamine A, was synthesized by alkylation of 4,7-dimethoxyindole 3 with 1,2-dibromoethane followed by transformation into azide, reduction of the latter with trimethylphosphine in the presence of 2-(tert-butoxycarbonyloximino)-2-phenylacetonitrile and oxydative demethylation of the Boc-amine 6 with silver(II) oxide. Quinone 8 was then treated in situ with the thiazole o-quinodimethane 10 to afford a regioisomeric mixture of the tetracyclic quinones 11. Treatment of the mixture with trifluoroacetic acid and molecular sieves 4-A provided the corresponding quinoneimines 12. Separation of the regioisomers was performed by preparative thin-layer chromatography on silica gel. The structural assignment was made by 2D 1H-13C HMBC correlations performed on the less polar regioisomer 12b. In vitro anti-leishmanial assays showed that the tested compounds possess a good potency towards two Leishmania sp. as well as against a virulent strain of Toxoplasma gondii and without any cytotoxicity against THP-1 cells.
Bioorganic & Medicinal Chemistry 09/2003; 11(16):3407-12. · 2.92 Impact Factor
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ABSTRACT: The synthesis of tetracyclic quinones 10a,b, 14a,b, 19a,b and 20a,b is described. The preparations involve regioselective Diels-Alder reactions via trapping the thiazole o-quinodimethane 9 with several benzofuranquinones and benzothiophenequinones. The structure of the regioisomers was assigned through 2D NMR 1H-13C HMBC experiments performed on 10a and 14a. Compounds 10a,b, 14a as well as phenol 1 and the starting quinones 2, 5, 7 and 15 are evaluated against Leishmania sp., Toxoplasma gondii and THP-1 cells. Almost all the tested compounds exhibit significant antiprotozoal activities with lower cytotoxicities than the reference compounds. Among them, quinones 2 and 14a possess the best activities towards L. donovani and T. gondii with the lowest toxicities.
Bioorganic & Medicinal Chemistry 06/2003; 11(10):2175-82. · 2.92 Impact Factor
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ABSTRACT: Quinonic derivatives were tested against a virulent RH strain of Toxoplasma gondii maintained in cell culture in THP-1, a human myelomonocytic cell line. The derivatives were tested at various doses (0.5-4 microg/ml) and compared with the reference molecules clindamycine, sulfadiazine, pyrimethamine and atovaquone. The percentage of parasite growth inhibition was observed after 72 h of incubation. The tested derivatives are bicyclic, tricyclic or tetracyclic quinones. Eight of these compounds exhibit over 70% inhibition of parasite growth; and two were nearly equipotent to pyrimethamine. These data indicate that the most active compounds against the RH strain of T. gondii are bis-heterocyclic quinones.
Parasitology Research 12/2002; 88(11):969-71. · 2.15 Impact Factor
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ABSTRACT: Pyrazinoindoloquinone 6 was synthesized by alkylation of ethyl 4,7-dimethoxyindole-2-carboxylate (1), followed by cyclization of the N-bromoethyl derivative 2b in the presence of ammonia. Oxidative demethylation of 2b and of the oxopyrazinoindole 3 with silver(II) oxide furnished quinones 5b and 6. Reduction of 3 with lithium aluminium hydride in dioxane provided 4, which was oxidized to afford 7. Quinones 5b, 6, and 7 were then treated in situ with the thiazole o-quinodimethane 9 to afford regioisomeric mixtures of the tetracyclic quinones 10 or the pentacyclic derivatives 11 or 12. The structural assignment was made by 2D NMR 1H-13C HMBC correlation performed on the major regioisomer 10a. In vitro antileishmanial assays showed that dimethoxyindole 2a and quinones 12a + 12b possess good inhibitory activity against two Leishmania sp. without any cytotoxicity towards a THP-1 cell line. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)
Annalen der Chemie und Pharmacie 11/2002; 2002(23):4005 - 4010. · 3.10 Impact Factor
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ABSTRACT: The Diels–Alder reaction between a thiazole o-quinodimethane and 4,6-dichloroquinoline-5,8-dione gave 6-chloro-9-azaanthra[2,3-b]thiazole-5,10-dione as a single regioisomer. Its structure was assigned by 2D 1H–13C HMBC short- and long-range correlations. Measuring the spectra in CF3CO2D indicated that both nitrogen atoms of pyridine and thiazole rings are deuterated. Copyright © 2001 John Wiley & Sons, Ltd.
Magnetic Resonance in Chemistry 12/2001; 40(2):165 - 167. · 1.44 Impact Factor
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ABSTRACT: 4-(Bromomethyl)-5-(dibromomethyl)thiazole (1) was prepared in good yields by bromination of 4,5-dimethylthiazole with 3.3 equiv of NBS in the presence of AIBN. Treatment of 1 with sodium iodide led to a thiazole o-quinodimethane 2 which was trapped in situ with dienophiles such as N-phenylmaleimide, DMAD, or acrylate derivatives. From the latter, 6-substituted-4,5-dihydrobenzothiazoles 7 are selectively formed. Anthra[2,3-b]thiazole-4,5-diones 13-15 were obtained from naphthoquinones. With 2- or 3-bromonaphthoquinones (11 or 12), the cycloadditions were found highly regioselective. Structural assignment of the regioisomers was made by a 2D (1)H-(13)C HMBC technique performed on the aromatized cycloadduct 15b. Calculations of HOMO and LUMO frontier orbital coefficients by the semiempirical PM3 method show that the regiochemistry observed in the cycloadditions of 2 toward acrylate dienophiles or naphthoquinones 11 and 12 did not agree with the corresponding values.
The Journal of Organic Chemistry 02/1997; 62(2):405-410. · 4.45 Impact Factor
